ACR: Fibromyalgia a Recognized Disorder but Misconceptions Linger

by John Gever John Gever,Contributing Writer, MedPage Today
November 12, 2007

BOSTON, Nov. 12 -- Approval this summer of the first drug to treat fibromyalgia legitimized the condition as a distinct illness, but patients still face challenges, including physician acceptance, doctors said here.

It has now been firmly proven that the condition is primarily a disorder of pain signaling, arising in the central nervous system, Daniel Clauw, M.D., of the University of Michigan in Ann Arbor, told attendees at an industry-funded symposium held in conjunction with the American College of Rheumatology meeting.

Nevertheless, he said, many physicians, including specialists, still regard the local manifestations, such as tender points, as important, creating what he called "a circular problem" in treatment.

Among the classic symptoms of fibromyalgia is abnormal pain in some or all of 18 points in the body when touched. The American College of Rheumatology has developed criteria for diagnosing the condition that includes a finding that at least 11 of these points are tender.

But, "the longer we keep publishing review articles [with illustrations of] a woman with 18 dots," Dr. Clauw said, "the longer people are going to think there's something wrong in those 18 areas of the body, even though we know that's not the case."

Dr. Clauw said it is better to think of fibromyalgia as a disorder of the pain-sensation system's "volume control" that determines how the brain processes touch stimuli.

"This is likely set by the genes we are born with, and modified by the environment," he said. Those with a high volume control setting will feel more pain for a given level of stimulus.

Consequently, he said, one can test for fibromyalgia with stimuli elsewhere than the classical 18 points, such as the thumbnail. He said fibromyalgia can also be diagnosed without touching patients at all.

Don Goldenberg, M.D., of Tufts University School of Medicine in Boston, illustrated the dual role of genetics and environment in the disorder. "Fifty percent of my patients say they were born with it, had it since they were kids. The rest say something happened" to trigger it.

Dr. Clauw noted the wide range of events that appear to trigger fibromyalgia, such as infections and injuries. A small subset of people experiencing these events will go on to develop regional or widespread pain syndromes as a result, he said, because of their particular genetic makeup.

Getting effective treatment to fibromyalgia patients is important because when they have had uncontrolled symptoms for too long, they become resistant to treatment, he said.

"They're distressed because they can't function normally in their societal roles, they become depressed because of what the pain and fatigue has done to their life, they develop ways of thinking [confirmed by brain imaging] that can actually increase their pain levels by changing the way pain is transmitted in the brain, they develop bad habits that are called 'maladaptive illness behaviors' where they make their condition worse," Dr. Clauw said.

Fortunately, according to Dr. Goldenberg, many drugs as well as nondrug therapies are available to make fibromyalgia sufferers more comfortable.

Among them are exercise, certain analgesics, some classes of antidepressants and, most recently, drugs mainly considered as anticonvulsants.

However, opioids and most over-the-counter analgesics are not effective in fibromyalgia, he said. The most reliable analgesic is tramadol combined with acetaminophen.

Amitryptyline has been found modestly effective in four placebo-controlled trials, he said, while cyclobenzaprine was effective in two out of four placebo-controlled trials.

Equivocal results have come out of studies of selective serotonin reuptake inhibitors such as fluoxetine (Prozac).

But antidepressants affecting both serotonin and norepinephrine have shown good results, Dr. Goldenberg said. Duloxetine (Cymbalta) and milnacipran (Ixel) both show promise in this condition.

Then there are the anticonvulsants. Pregabalin (Lyrica) is now the only medication approved in the United States to treat fibromyalgia, although applications are in the works for duloxetine and milnacipran.

Lee Simon, M.D., of Harvard, said the FDA is making it easier for new products to be approved for fibromyalgia.

Dr. Simon, until recently an FDA division director, said the agency was developing new standards to guide development of new agents. These are not yet fully in place in the form of guidance documents, he said, but the pathway is now apparent from recent decisions.

The FDA is now focusing on how well new agents work against pain as reported by patients, he said. But drug developers will also need to measure functional outcomes and patients' global self-assessments.

All three response categories will need to be included in trials "either as co-primary outcomes or as composites per patient response," he said.

He said an ideal way to express this would be as the percentage of patients who meet predetermined criteria for an adequate response.

Dr. Simon highlighted a problem for clinicians looking for the best treatments for individual patients: that the literature on drugs is dominated by clinical trials conducted to support approval applications.

"Regulatory trials for approval are not the same thing as a clinical trial to understand how to use a drug in the real clinical world," he cautioned.

Even the diagnostic criteria developed by specialty and other groups were developed at least in part to support clinical trials, so that results from different trials could be compared. "It's not clear that this is correct for diagnosis," Dr. Simon said.

Nevertheless, he urged physicians looking for unbiased information about drugs to rely primarily on the FDA-approved label, even though it is based mainly on regulatory trial data.

He also warned against relying exclusively on treatment management algorithms, even those based on randomized controlled trials.

"The individual patient has individual potential risks and potential benefits," he said. "What has eluded government and eluded managed care is that algorithmic medicine, although a nice way to give you parameters of choice, is not appropriate for the individual patient, as opposed to the population."

Added Dr. Simon, "It's very true for fibromyalgia."

The symposium was sponsored for CME credit by the University of Kentucky College of Medicine and supported by an unrestricted educational grant from Forest Pharmaceuticals.

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